Rapid expansion of the brain of early embryos begins shortly after the neural tube is established by the process of neurulation. Concomitantly, the lumen of most of the length of the spinal cord becomes occluded; that is, the lateral walls of the cord come into apposition, temporarily obliterating the lumen. Neural tube fluid pressure is required for normal expansion of the brain and we hypothesize that occlusion has an important role in brain expansion by localizing and confining neural tube fluid to principally brain regions. The objectives of this proposed project are to determine when and where occulusion and reopening of the spinal cord occur, what structural changes characterize these processes, how occlusion and reopening occur and whether brain enlargement is normal in embryos containing open neural tube defects (myeloschisis) caudal to the area of occlusion. By meeting these objectives, our understanding of the early morphogenesis of the brain of normal embryos will be greatly enhanced, and insight should be gained into how morphogenesis can go awry, resulting in certain major anomalies of the central nervous system.